Cadmium toxicity, noted in rodents during late gestation, has been compared with preeclampsia, a rendition associated with an imbalance between thromboxane A(2) and prostacyclin. This study examines the effect of cadmium on the human placental production of thromboxane A(2) and prostacyclin, as reflected by their hydrolysis products (TxB(2), 6-keto-PGF(1 alpha)), Following two 12-h exposures, 6-keto-PGF(1 alpha) production by placental explants was 74.8 and 39.9% of unexposed tissue values at 40 and 100 mu M cadmium, respectively, with no significant effect on TxB(2). The effect of glutathione on placental TxB(2) and 6-keto-PGF(1 alpha) production was also examined, Sulfhydryl concentrations have been shown to affect thromboxane and prostacyclin production, and glutathione binds to cadmium reducing its toxicity, Although glutathione at concentrations up to 1 mM had no effect on explant function, glutathione did prevent the effects of cadmium on 6-keto-PGF(1 alpha) This study indicates that acute exposure to cadmium at high concentrations directly affects the placental production of 6-keto-PGF(1 alpha), disturbing the thromboxane A(2)/prostacyclin ratio.